Diffusion-weighted imaging (DWI), in which contrast is based on changes in water apparent diffusion coefficient (ADC), is a powerful imaging modality for early detection of ischemic brain injury. During the acute phase of stroke, the anatomical region defined on the DWI is initially smaller than the area of cerebral-blood-flow (CBF) deficit, but this region expands and eventually coincides with the area defined on perfusion-weighted imaging (PWI). The difference in the anatomic area defined by part PWI and DWI, often referred to as the "perfusion-diffusion" mismatch, may represent salvageable tissues (i.e., the ischemic penumbra). Animal stroke imaging, however, has been done exclusively under anesthetized conditions to eliminate movement artifacts. Anesthesia has a powerful influence on neuronal activity, cerebral circulation, neural-vascular coupling, and stroke outcome. An awake stroke model for imaging studies without the confound of anesthesia has the potential to better model the clinical conditions where most patients have a stroke while conscious and under considerable stress. Recent advances have made imaging of awake animals feasible. The general aim of this proposal is to use quantitative perfusion, diffusion and functional imaging to characterize tissue fate in focal ischemic brain injury in an awake stroke model (permanent, 30-, 60- or 90- rain temporary occlusion), and to relate the derived tissue fate to functional status and an index of neuronal cell death (H&E staining). Ischemia induction, reperfusion and imaging will be carried out on awake rats acclimated to a restrainer to minimize stress. Parallel studies under anesthesia will be carried out for comparison. Quantitative perfusion, diffusion and functional imaging at 175x175x1500 mu/m3 a resolution will be acquired every 30 mins up to 4 hrs, again at 24 and 72 hrs on a 4.7T scanner. Our overall hypothesis is that the "'perfusion-diffusion" mismatch, its spatiotemporal dynamics, tissue fates and functional status on a pixel-by-pixel basis will deteriorate to a larger extent and faster in the awake compared to anesthetized animals, potentially leading to different "clock window" and "tissue signature "for therapeutic intervention.